"The purpose of this project is to develop diagnostic tools that will enable population-based early cancer detection. This effort arises out of a long term collaboration with investigators at Hopkins that led to a report in 1988 that showed we could improve the diagnosis of early lung cancer using a sputum-based immunodetection assay. We have continued that work by conducting two prospective validation trials. The initial results of those studies have been published and suggest that the test correctly finds at least two thirds of the lung cancer cases well in advance of any other evidence of the cancer. To determine if this approach is appropriate for broader application, we are working under a CRADA mechanism with the company, Chiron (Bayer Diagnostics), Johns Hopkins, the University of South Florida as well as the institutions of the Lung Cancer Early Detection Working Group to refine this diagnostic technology for population-based application. In a series of papers, we describe the potential basis for the success of this assay. We have found that the target marker recognized by the antibody is the molecule, heterogeneous nuclear, ribonucleoprotein A2/B1 (hnRNP). The distribution of that marker is surprisingly diffuse in the airways of former lung cancer patients with high levels of antigen expression found in both normal and pre invasive airway cells. We have also found that the timing and pattern of expression of hnRNP in developing lungs is consistent with this molecule playing a role in early lung development. Another group in England using this antibody for early lung cancer detection has recently reported diagnostic accuracy with the immunostaining approach similar to our previous studies. Work on understanding the biological basis for routine early lung cancer detection continues." "As part of the CRADA mechanism, we are working with Chiron to develop an efficient diagnostic instrumentation platform to handle the analysis of the sputum specimens in a cost-effective way. Developing such a capability would allow us to more routinely detect airway-confined lung cancer, which may be controlled by aerosolized chemoprevention agents. The ultimate goal of this development project is to identify useful and economical analytical tools that provide a comprehensive picture about the status of the carcinogen-exposed epithelium."